Cardiovascular disease is the disease with the highest mortality rate in China, accounting for more than 40% of the disease deaths of residents. As the most common acute cardiovascular disease in the clinic, acute myocardial infarction has a high incidence and a large risk of death, and with the advancement of China’s aging process, its incidence and mortality will show a significant upward trend.
The research team led by Professor Ge Junbo and Professor Sun Aijun, academician of the Chinese Academy of Sciences and director of the Department of Cardiology of Zhongshan Hospital affiliated to Fudan University, improved cardiac repair by promoting the clearance and degradation of apoptosis cardiomyocytes after myocardial infarction. Recently, the relevant research results were published in the journal “Circulation”.
Schematic diagram of maintaining the role of cell burial Courtesy of the interviewee
The role of cell burial is the process of processing and degrading apoptotic cells by phagocytes. After myocardial infarction occurs, phagocytes dominated by macrophages play a “endocytosis” role by recognizing signals such as “find me” and “eat me” expressed by apoptotic cardiomyocytes, clearing and degrading apoptotic cardiomyocytes, thereby reducing inflammatory response and promoting damaged tissue repair.
“After myocardial ischemia, cardiomyocytes undergo necrosis and apoptosis, and a large number of dead cardiomyocytes require macrophages to efficiently and continuously ingest and remove these cell debris, however, the mechanism that regulates the continuous removal and degradation of contents by macrophages remains unknown.” Ge Junbo told China Science Daily.
Cysteine proteases (CP) are a class of proteolytic enzymes containing cysteine residues, including aspartate-specific cysteine proteases, histases, calpain, and pod proteins (Lgmn). Lgmn is a highly specific asparagine acyl endopeptase located in macrophage lysosomes. As a member of the CP family, Lgmn, in addition to being involved in regulating cell proliferation and apoptosis like other family members, also plays an important role in mediating immune inflammation.
The study shows that Lgmn is involved in myocardial reconstruction after myocardial ischemic injury. Lgmn is a gene specifically expressed by cardiac in situ macrophages. Lgmn deficiency led to a significant deterioration of cardiac function in mice after myocardial infarction, accompanied by the accumulation and infarction of apoptotic cardiomyocytes, and the ability of macrophages in the border region to devour dead cardiomyocytes gradually decreased.
Further studies have found that Lgmn deficiency makes in situ macrophage intracellular calcium mobilization ability defective, resulting in a decrease in cytoplasmic calcium, so when cytometic calcium-deficient macrophages engulf apoptotic cardiomyocytes again, the formation of lysosomes around the engulfed heart muscle cell fragments is inhibited, and the continuous and efficient phagocytic degradation process of dead cardiomyocytes is inhibited.
The findings directly link high-efficiency burial effects to cardiac wound healing and identify Lgmn as an important molecule that affects the resolution of inflammation and heart function repair in acute myocardial infarction. This is of great guiding significance for avoiding the expansion of myocardial infarction area and reducing the loss of cardiomyocytes. (Source: China Science Daily, Zhang Shuanghu, Huang Xin)
Related paper information:https://doi.org/10.1161/CIRCULATIONAHA.121.056640
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